Malaria is the most important vector-borne disease in Southeast Asia. Malaria control in this region faces a number of important challenges, including a lack of information on malaria incidence in remote impoverished areas, a lack of knowledge and viable methods to prevent malaria introduction from hyperdendemic countries to neighboring low-incidence countries, and a lack of effective, integrated control strategies. We strategically select study sites in China, Thailand and Myanmar that vary significantly in malaria endemicity. Malaria parasite introduction from Myanmar by human travelers, together with local transmission heterogeneity, represents the most difficult problem for malaria control in these countries. Therefore, the overarching objective of this project is to gain critical information on intra-country and inter-country malaria epidemiology for developing effective malaria control strategies in these countries. We design the following five specific aims: 1) to conduct malaria surveillance to determine clinical malaria incidence and sub-clinical infection rates in remote, impoverished border regions and other sentinel sites, and to examine inter-country transmission dynamics; 2) to study the molecular epidemiology of antimalarial drug resistance and the population genetic structure of Plasmodium falciparum and P. vivax; 3) to identify malaria transmission foci at high spatial resolution and determine key environmental and biological determinants for transmission foci in the era of an intensive antimalarial campaign; 4) to examine immuno-epidemiology of P. falciparum and P. vivax infections using high-throughput protein microarrays, and 5) to develop integrated malaria management strategies and systematically evaluate the entomological and epidemiological impacts in multiple sites with distinct malaria epidemiology. This project lays important foundations for other projects of the ICEMR program, and will provide critical knowledge for developing and evaluating integrated malaria management strategies.